Two model systems of cell differentiation in vitro, a mouse teratocarcinoma and a human promyelocytic leukemia cell lines, will be used to investigate the effect of retinoic acid on the regulation of gene expression. We intend to use recombinant DNA vectors containing either the genome of SV40 or polyoma virus or kirsten sarcoma virus and a series of monoclonal antibodies lineage specific to elucidate the mechanisms involved in the regulation of differential gene expression in stem vs retinoic acid induced differentiated cells. In particular the translational and pretranslational level of expression of the tumor virus vectors after transformation of TK deficient cells, the DNase I sensitivity of the chromatin, and the relationship between methylation and gene activity will be investigated in mouse teratrocarcinoma derived stem and retinoic acid induced differentiated cells. The coordinate expression of lineage specific genes at different stages of myeloid differentiation, the identification of the structure and function of such genes, the cloning of the mRNAs for studies on transcriptional or posttranscriptional regulation, the role played by the transferrin receptor and its possible interaction with retinoic acid will be investigated in human HL60 promyelocytic leukemia cells.